Many disease states lead to disorders of mucosal membranes. One of the more common mucosal membrane disorders is interstitial cystitis. Interstitial cystitis is a poorly understood bladder condition for which there is no universal effective treatment program (Fleischmann, J. D. et al. 1991. J. Urology, 146:1235). Symptoms include urgency for urination, increased frequency of urination and suprapubic pain usually relieved by voiding. Other symptoms include arthritis, spastic colon and low grade fever. Individuals with interstitial cystitis can be significantly disabled, and individuals with advanced interstitial cystitis can require major surgery in order to function.
There is no standard treatment for interstitial cystitis. Among the treatments used are hydraulic distention of the bladder, oral amitriptyline or sodium pentosanpolysulfate, intravesical instillation of dimethylsulfoxide, oxychlorosene sodium, silver nitrate, heparin, or of a composition comprising an angiostatic steroid and pentosanpolysulfate. However, both the efficacy and the effectiveness of these treatments is variable.
Hydraulic distention of the bladder is done under general or spinal anesthesia for one to two minutes at a pressure of 80 to 100 cm H2O. In one study using hydraulic distention of the bladder to treat interstitial cystitis, less than 55% of the patients treated reported relief immediately after treatment and only 2% reported relief six months after treatment (Hanno P. M. et al. 1991. Semin Urology, 9:143).
Instillation of dimethylsulfoxide (DMSO) into the bladder for six to eight weeks resulted in a 53% response rate to DMSO versus an 18% response rate to placebo, with the average length of response being six months (Perez-Marrero, R. et al. 1967. J. Urology, 98: 671). Pharmacological effects of DMSO include membrane penetration, enhanced drug absorption, anti-inflammatory and analgesic effects, collagen dissolution, muscle relaxation and mast cell histamine release. Side effects include increased vesicle irritability and garlic-like breath odor.
Equivalent results to instillation of DMSO have been reported with oxychlorosene sodium (Messing, E. M. et al. 1978. Urology, 12:381). However, instillation of oxychlorosene sodium requires anesthesia because of intense discomfort.
While interstitial cystitis is an important disorder that may cause disruption or irritation of the mucosal membranes, other conditions, such as colitis, Crohn's disease and even some forms of cancer, such as bladder cancer, also appear to cause similar problems.
Therefore, there is a need for a therapeutic agent for the treatment of interstitial cystitis and other conditions which affect the mucosal membranes with improved efficacy, without major surgery, undesirable side effects, or intense physical discomfort.
Accordingly, it is an object of the present invention to provide a method for treating a disorder of a mucosal membrane such as bladder cancer, Crohn's disease or colitis, lung cancer, pulmonary and respiratory diseases, gynecological malignancies and cancer of the mouth.
Another object of the invention is to provide a method for treating a subject suffering from interstitial cystitis.
It is also an object of the invention to provide a pharmaceutical composition acceptable for administration via, for example, catheter or enema.
A further object of the invention is to provide novel sulfated chitinous polymers.
These and other objects, features, and advantages of the invention will be apparent from the following description and claims.